{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:52:22Z","timestamp":1767772342600,"version":"3.41.2"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2020.00620","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T04:46:26Z","timestamp":1586925986000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Tolerance to FVIII: Role of the Immune Metabolic Enzymes Indoleamine 2,3 Dyoxigenase-1 and Heme Oxygenase-1"],"prefix":"10.3389","volume":"11","author":[{"given":"Davide","family":"Matino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sajjad","family":"Afraz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Tieu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Gargaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Fallarino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Iorio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.7326\/M19-1208","article-title":"Establishing the prevalence and prevalence at birth of hemophilia in males: a meta-analytic approach using national registries.","volume":"171","author":"Stonebraker","year":"2019","journal-title":"Ann Intern Med"},{"key":"B2","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.3324\/haematol.2019.221093","article-title":"Hemophilia A and B: molecular and clinical characteristics of similar, but different diseases.","volume":"104","author":"Castaman","year":"2019","journal-title":"Haematologica"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1160\/TH16-01-0049","article-title":"The burden of inhibitors in haemophilia patients.","volume":"116","author":"Walsh","year":"2016","journal-title":"Thromb Haemost"},{"key":"B4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/rth2.12094","article-title":"Product type and other environmental risk factors for inhibitor development in severe hemophilia A.","volume":"2","author":"Peyvandi","year":"2018","journal-title":"Res Pract Thromb Haemost"},{"key":"B5","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1111\/hae.13075","article-title":"Non\u2212genetic risk factors in haemophilia A inhibitor management\u2013the danger theory and the use of animal models.","volume":"22","author":"L\u00f6vgren","year":"2016","journal-title":"Haemophilia"},{"key":"B6","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1182\/blood-2008-02-124941","article-title":"Dynamics of factor VIII interactions determine its immunologic fate in hemophilia a.","volume":"112","author":"Lacroix-Desmazes","year":"2008","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1055\/s-0038-1657777","article-title":"Inhibitor formation in congenital hemophilia A: an immunological perspective.","volume":"44","author":"Delignat","year":"2018","journal-title":"Semin Thromb Hemost"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2922","DOI":"10.1182\/blood-2011-09-379453","article-title":"F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis.","volume":"119","author":"Gouw","year":"2012","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1006\/smim.2000.0230","article-title":"How does the immune system distinguish self from nonself?","volume":"12","author":"Medzhitov","year":"2000","journal-title":"Sem Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006957","article-title":"Hogquist KAT-. cell tolerance: central and peripheral.","volume":"4","author":"Xing","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1111\/j.1538-7836.2009.03314.x","article-title":"Induction of factor VIII\u2212specific unresponsiveness by intrathymic factor VIII injection in murine hemophilia A.","volume":"7","author":"Madoiwa","year":"2009","journal-title":"J Thromb Haemost"},{"key":"B12","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1055\/s-0037-1614081","article-title":"Sensitization of CD4+ T cells to coagulation factor VIII: response in congenital and acquired hemophilia patients and in healthy subjects.","volume":"84","author":"Reding","year":"2000","journal-title":"Thromb Haemost"},{"key":"B13","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1046\/j.1538-7836.2003.00366.x","article-title":"Recognition of coagulation factor VIII by CD4+ T cells of healthy humans.","volume":"1","author":"Hu","year":"2003","journal-title":"J Thromb Haemost"},{"key":"B14","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1182\/bloodadvances.2017008706","article-title":"CD4 T cells specific for factor VIII are present at high frequency in healthy donors and comprise na\u00efve and memory cells.","volume":"1","author":"Meunier","year":"2017","journal-title":"Blood Adv"},{"key":"B15","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1182\/blood-2002-05-1369","article-title":"CD4+ T-cell clones specific for wild-type factor VIII: a molecular mechanism responsible for a higher incidence of inhibitor formation in mild\/moderate hemophilia A.","volume":"101","author":"Jacquemin","year":"","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1182\/blood-2012-07-444877","article-title":"Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients.","volume":"121","author":"Whelan","year":"2013","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1182\/blood-2014-09-598268","article-title":"Affinity of FVIII-specific antibodies reveals major differences between neutralizing and nonneutralizing antibodies in humans.","volume":"125","author":"Hofbauer","year":"2015","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1182\/blood.V95.11.3435","article-title":"Antibodies to the FVIII light chain that neutralize FVIII procoagulant activity are present in plasma of nonresponder patients with severe hemophilia A and in normal polyclonal human IgG.","volume":"95","author":"Moreau","year":"","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S1074-7613(04)00111-6","article-title":"Back to central tolerance.","volume":"20","author":"Mathis","year":"2004","journal-title":"Immunity"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1817","article-title":"Mechanisms maintaining peripheral tolerance.","volume":"11","author":"Mueller","year":"2010","journal-title":"Nat Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1084\/jem.20082394","article-title":"Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity.","volume":"206","author":"Ohnmacht","year":"2009","journal-title":"J Exp Med"},{"key":"B22","article-title":"Crystal structure of human heme oxygenase-1.","volume":"6","author":"Schuller","year":"1999","journal-title":"Nat Struct Mol Biol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1124\/pr.107.07104","article-title":"Pharmacological and clinical aspects of heme oxygenase.","volume":"60","author":"Abraham","year":"2008","journal-title":"Pharmacol Rev"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-60761-869-0_18","article-title":"Immunoregulatory properties of heme oxygenase-1.","author":"Blancou","year":"2010","journal-title":"Suppression and Regulation of Immune Responses. Methods in Molecular Biology (Methods and Protocols)"},{"key":"B25","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S0002-9440(10)63365-2","article-title":"Heme oxygenase-1 modulates early inflammatory responses.","volume":"165","author":"Kapturczak","year":"2004","journal-title":"Am J Pathol"},{"key":"B26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1172\/JCI4165","article-title":"Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency.","volume":"103","author":"Yachie","year":"1999","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.2353\/ajpath.2007.070096","article-title":"Heme oxygenase-1 attenuates ovalbumin-induced airway inflammation by up-regulation of foxp3 T-regulatory cells, interleukin-10, and membrane-bound transforming growth factor- 1.","volume":"171","author":"Xia","year":"2007","journal-title":"Am J Pathol"},{"key":"B28","doi-asserted-by":"crossref","first-page":"5936","DOI":"10.4049\/jimmunol.177.9.5936","article-title":"Heme oxygenase-1-mediated CD4+CD25high regulatory T cells suppress allergic airway inflammation.","volume":"177","author":"Xia","year":"2006","journal-title":"J Immunol"},{"key":"B29","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1111\/j.1600-0625.2007.00581.x","article-title":"Heme oxygenase-1 inhibits T cell-dependent skin inflammation and differentiation and function of antigen-presenting cells.","volume":"16","author":"Listopad","year":"2007","journal-title":"Exp Dermatol"},{"key":"B30","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1172\/JCI28844","article-title":"Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation.","volume":"117","author":"Chora","year":"2007","journal-title":"J Clin Invest"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-28488-6","article-title":"Naturally derived Heme-Oxygenase 1 inducers attenuate inflammatory responses in human dendritic cells and T cells: relevance for psoriasis treatment.","volume":"8","author":"Campbell","year":"2018","journal-title":"Sci Rep"},{"key":"B32","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1182\/blood-2005-02-0494","article-title":"Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression.","volume":"106","author":"Chauveau","year":"2005","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.4049\/jimmunol.0802436","article-title":"Carbon monoxide inhibits TLR-induced dendritic cell immunogenicity.","volume":"182","author":"R\u00e9my","year":"2009","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2682","DOI":"10.1182\/blood-2009-04-216408","article-title":"Induction of heme oxygenase-1 in factor VIII\u2013deficient mice reduces the immune response to therapeutic factor VIII.","volume":"115","author":"Dimitrov","year":"2010","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1111\/j.1538-7836.2009.03571.x","article-title":"Splenic marginal zone antigen\u2212presenting cells are critical for the primary allo\u2212immune response to therapeutic factor VIII in hemophilia A.","volume":"7","author":"Navarrete","year":"2009","journal-title":"J Thromb Haemost"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1182\/blood-2008-01-133181","article-title":"Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo.","volume":"112","author":"van Schooten","year":"2008","journal-title":"Blood"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.3324\/haematol.2013.084665","article-title":"Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter.","volume":"98","author":"Repess\u00e9","year":"2013","journal-title":"Haematologica"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.30.341","article-title":"Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis.","volume":"30","author":"Brydun","year":"2007","journal-title":"Hypertens Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.139","article-title":"Immunometabolism in 2017: driving immunity: all roads lead to metabolism.","volume":"18","author":"Pearce","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s41573-019-0016-5","article-title":"Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond.","volume":"18","author":"Platten","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"B41","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1097\/01.PSY.0000078188.74020.CC","article-title":"Tryptophan as a link between psychopathology and somatic states.","volume":"65","author":"Russo","year":"2003","journal-title":"Psychosom Med"},{"key":"B42","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S1471-4906(03)00072-3","article-title":"Tolerance, DCs and tryptophan: much ado about IDO.","volume":"24","author":"Grohmann","year":"2003","journal-title":"Trends Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nri1457","article-title":"IDO expression by dendritic cells: tolerance and tryptophan catabolism.","volume":"4","author":"Mellor","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1007\/s00726-010-0787-9","article-title":"Kynurenine metabolism in health and disease.","volume":"41","author":"Kolodziej","year":"2011","journal-title":"Amino Acids"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/ni1003","article-title":"Modulation of tryptophan catabolism by regulatory T cells.","volume":"4","author":"Fallarino","year":"2003","journal-title":"Nat Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nature06471","article-title":"Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease.","volume":"451","author":"Romani","year":"2008","journal-title":"Nature"},{"key":"B47","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cytogfr.2017.05.004","article-title":"Amino-acid sensing and degrading pathways in immune regulation.","volume":"35","author":"Grohmann","year":"2017","journal-title":"Cytokine Growth Factor Rev"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2077","article-title":"Indoleamine 2, 3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells.","volume":"12","author":"Pallotta","year":"2011","journal-title":"Nat Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/nature13323","article-title":"Aryl hydrocarbon receptor control of a disease tolerance defence pathway.","volume":"511","author":"Bessede","year":"2014","journal-title":"Nature"},{"key":"B50","doi-asserted-by":"publisher","first-page":"6752","DOI":"10.4049\/jimmunol.176.11.6752","article-title":"The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor \u03b6-chain and induce a regulatory phenotype in naive T cells.","volume":"176","author":"Fallarino","year":"2006","journal-title":"J Immunol"},{"key":"B51","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.4049\/jimmunol.177.4.2061","article-title":"1-Methyl-tryptophan can interfere with TLR signaling in dendritic cells independently of IDO activity.","volume":"177","author":"Agaugu\u00e9","year":"2006","journal-title":"J Immunol"},{"key":"B52","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00109-007-0262-6","article-title":"IDO-. expressing regulatory dendritic cells in cancer and chronic infection.","volume":"86","author":"Popov","year":"2008","journal-title":"J Mol Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2874","article-title":"High doses of CpG oligodeoxynucleotides stimulate a tolerogenic TLR9\u2013TRIF pathway.","volume":"4","author":"Volpi","year":"2013","journal-title":"Nat Commun"},{"key":"B54","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1002\/eji.200737184","article-title":"On watching the watchers: IDO and type I\/II IFN.","volume":"37","author":"Puccetti","year":"2007","journal-title":"Eur J Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/nm1563","article-title":"Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy.","volume":"13","author":"Grohmann","year":"2007","journal-title":"Nat Med"},{"key":"B56","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.trim.2015.05.003","article-title":"IDO expressing dendritic cells suppress allograft rejection of small bowel transplantation in mice by expansion of Foxp3 + regulatory T cells.","volume":"33","author":"Xie","year":"2015","journal-title":"Transpl Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1182\/blood.v110.11.1344.1344","article-title":"The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation.","volume":"110","author":"Chen","year":"2007","journal-title":"Blood"},{"key":"B58","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1158\/2326-6066.CIR-14-0137","article-title":"Extensive pro fi ling of the expression of the indoleamine 2, 3-dioxygenase 1 protein in normal and tumoral human tissues.","volume":"3","author":"Baren Van","year":"2015","journal-title":"Cancer Immunol Res"},{"key":"B59","doi-asserted-by":"publisher","first-page":"6743","DOI":"10.1021\/acs.biochem.6b01005","article-title":"Analysis of reaction intermediates in tryptophan 2,3-dioxygenase: a comparison with indoleamine 2,3-dioxygenase.","volume":"55","author":"Basran","year":"2016","journal-title":"Biochemistry"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1007\/s00726-014-1766-3","article-title":"Human indoleamine 2, 3-dioxygenase-2 has substrate specificity and inhibition characteristics distinct from those of indoleamine.","volume":"46","author":"Ball","year":"2014","journal-title":"Amino Acids"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1038\/nm934","article-title":"Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase.","volume":"9","author":"Uyttenhove","year":"2003","journal-title":"Nat Med"},{"key":"B62","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1084\/jem.20020052","article-title":"Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites.","volume":"196","author":"Terness","year":"2002","journal-title":"J Exp Med"},{"key":"B63","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.immuni.2005.03.013","article-title":"GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase.","volume":"22","author":"Munn","year":"2005","journal-title":"Immunity"},{"key":"B64","doi-asserted-by":"publisher","first-page":"5953","DOI":"10.4049\/jimmunol.1001628","article-title":"Upregulates regulatory t cells via tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis.","volume":"185","author":"Yan","year":"2010","journal-title":"J Immunol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"19961","DOI":"10.1073\/pnas.1014465107","article-title":"Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism.","volume":"107","author":"Nguyen","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B66","doi-asserted-by":"publisher","first-page":"3190","DOI":"10.4049\/jimmunol.0903670","article-title":"An interaction between kynurenine and the Aryl hydrocarbon receptor can generate regulatory T cells.","volume":"185","author":"Mezrich","year":"2010","journal-title":"J Immunol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2019.01973","article-title":"Engagement of nuclear coactivator 7 by 3-hydroxyanthranilic acid enhances activation of aryl hydrocarbon receptor in immunoregulatory dendritic cells.","volume":"10","author":"Gargaro","year":"2019","journal-title":"Front Immunol"},{"key":"B68","doi-asserted-by":"crossref","first-page":"356","DOI":"10.2337\/diabetes.51.2.356","article-title":"Indoleamine 2,3-dioxygenase expression in transplanted NOD islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes.","volume":"51","author":"Alexander","year":"2002","journal-title":"Diabetes"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1053\/j.gastro.2003.08.031","article-title":"Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene sulfonic acid colitis in mice.","volume":"125","author":"Gurtner","year":"2003","journal-title":"Gastroenterology"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00034","article-title":"Tryptophan-degrading enzymes in tumoral immune resistance.","volume":"6","author":"van Baren","year":"2015","journal-title":"Front Immunol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3324\/haematol.2018.206383","article-title":"Pathogenic immune response to therapeutic factor VIII: Exacerbated response or failed induction of tolerance?","volume":"104","author":"Varthaman","year":"2019","journal-title":"Haematologica"},{"key":"B72","doi-asserted-by":"publisher","first-page":"568","DOI":"10.2450\/2016.0252-16","article-title":"Summary report of the first international conference on inhibitors in haemophilia A.","volume":"15","author":"Lacroix-Desmazes","year":"2017","journal-title":"Blood Transfus"},{"key":"B73","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/gt.2009.13","article-title":"Indoleamine 2,3-dioxygenase attenuates inhibitor development in gene-therapy-treated hemophilia A mice.","volume":"16","author":"Liu","year":"2009","journal-title":"Gene Ther"},{"key":"B74","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1182\/blood-2010-06-289009","article-title":"Stimulation and inhibition of FVIII-specific memory B-cell responses by CpG-B (ODN 1826), a ligand for Toll-like receptor 9.","volume":"117","author":"Allacher","year":"2011","journal-title":"Blood"},{"key":"B75","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/nri2163","article-title":"IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-\u03baB activation.","volume":"7","author":"Puccetti","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"3766","DOI":"10.1172\/JCI81859","article-title":"IDO1 suppresses inhibitor development in hemophilia A treated with factor VIII.","volume":"125","author":"Matino","year":"2015","journal-title":"J Clin Invest"},{"key":"B77","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/jth.12065","article-title":"Dangerous liaisons: how the immune system deals with factor VIII.","volume":"11","author":"Wroblewska","year":"2013","journal-title":"J Thromb Haemost"},{"key":"B78","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1365-2516.2010.02231.x","article-title":"Non\u2212genetic risk factors and the development of inhibitors in haemophilia: a comprehensive review and consensus report.","volume":"16","author":"Astermark","year":"2010","journal-title":"Haemophilia"},{"key":"B79","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1146\/annurev.iy.12.040194.005015","article-title":"Tolerance, danger, and the extended family.","volume":"12","author":"Matzinger","year":"1994","journal-title":"Annu Rev Immunol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1365-2516.2010.02215.x","article-title":"Factor VIII\u2212specific B cell responses in haemophilia A patients with inhibitors.","volume":"16","author":"Van Helden","year":"2010","journal-title":"Haemophilia"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1189\/jlb.0306164","article-title":"DAMPs, PAMPs and alarmins: all we need to know about danger.","volume":"81","author":"Bianchi","year":"2007","journal-title":"J Leukoc Biol"},{"key":"B82","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1160\/TH05-11-0729","article-title":"Recombinant factor VIII and factor VIII-von Willebrand factor complex do not present danger signals for human dendritic cells.","volume":"96","author":"Pfistershammer","year":"2006","journal-title":"Thromb Haemost"},{"key":"B83","doi-asserted-by":"publisher","first-page":"4741","DOI":"10.1182\/blood-2008-10-186452","article-title":"A. role for thrombin in the initiation of the immune response to therapeutic factor VIII.","volume":"114","author":"Skupsky","year":"2009","journal-title":"Blood"},{"key":"B84","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1182\/blood-2012-02-412361","article-title":"Major determinant of the immunogenicity of factor VIII in a murine model is independent of its procoagulant function.","volume":"120","author":"Meeks","year":"2012","journal-title":"Blood"},{"key":"B85","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1111\/jth.12740","article-title":"Role of coagulation\u2212associated processes on factor VIII immunogenicity in a mouse model of severe hemophilia A.","volume":"12","author":"Gangadharan","year":"2014","journal-title":"J Thromb Haemost"},{"key":"B86","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1160\/TH14-09-0789","article-title":"Danger signal-dependent activation of human dendritic cells by plasma-derived factor VIII products.","volume":"114","author":"Miller","year":"2015","journal-title":"Thromb Haemost"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12579","article-title":"Haemarthrosis and arthropathy do not favour the development of factor VIII inhibitors in severe haemophilia A mice.","volume":"21","author":"Peyron","year":"2015","journal-title":"Haemoph Off J World Fed Hemoph"},{"key":"B88","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.1182\/blood-2006-11-056291","article-title":"Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study.","volume":"109","author":"Gouw","year":"2007","journal-title":"Blood"},{"key":"B89","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1365-2141.2005.05605.x","article-title":"Environmental risk factors for inhibitor development in children with haemophilia A: a case\u2013control study.","volume":"130","author":"Santagostino","year":"2005","journal-title":"Br J Haematol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1111\/j.1365-2516.2010.02422.x","article-title":"Treatment related factors and inhibitor development in children with severe haemophilia A.","volume":"17","author":"Maclean","year":"2011","journal-title":"Haemophilia"},{"key":"B91","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/hae.13756","article-title":"Consensus statements on vaccination in patients with haemophilia\u2014Results from the Italian haemophilia and vaccinations (HEVA) project.","volume":"25","author":"Santagostino","year":"2019","journal-title":"Haemophilia"},{"key":"B92","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1182\/blood-2015-11-679282","article-title":"Concurrent influenza vaccination reduces anti-FVIII antibody responses in murine hemophilia A.","volume":"127","author":"Lai","year":"2016","journal-title":"Blood"},{"key":"B93","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1111\/hae.13387","article-title":"Vaccinations are not associated with inhibitor development in boys with severe haemophilia A.","volume":"24","author":"Platokouki","year":"2018","journal-title":"Haemophilia"},{"key":"B94","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1111\/j.1538-7836.2007.02595.x","article-title":"Treatment characteristics and the risk of inhibitor development: a multicenter cohort study among previously untreated patients with severe hemophilia A.","volume":"5","author":"Gouw","year":"2007","journal-title":"J Thromb Haemost"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1111\/j.1538-7836.2011.04467.x","article-title":"Surgery and inhibitor development in hemophilia A: a systematic review.","volume":"9","author":"Eckhardt","year":"2011","journal-title":"J Thromb Haemost"},{"key":"B96","doi-asserted-by":"publisher","first-page":"4046","DOI":"10.1182\/blood-2012-09-457036","article-title":"Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study.","volume":"121","author":"Gouw","year":"2013","journal-title":"Blood"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v120.21.627.627","article-title":"Surgical injury alone does not provoke the development of factor VIII inhibitors in mouse models of hemophilia A.","volume":"120","author":"Moorehead","year":"2012","journal-title":"Blood"},{"key":"B98","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1111\/j.1365-2516.2009.02122.x","article-title":"New early prophylaxis regimen that avoids immunological danger signals can reduce FVIII inhibitor development.","volume":"16","author":"Kurnik","year":"2010","journal-title":"Haemophilia"},{"key":"B99","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1111\/hae.12666","article-title":"The EPIC study: a lesson to learn.","volume":"21","author":"Auerswald","year":"2015","journal-title":"Haemophilia"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.00620\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T21:57:08Z","timestamp":1615240628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.00620\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":99,"alternative-id":["10.3389\/fimmu.2020.00620"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.00620","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2020,4,15]]},"article-number":"620"}}